Airway inflammation is a principal feature of asthma and contributes to bronchial hyperresponsiveness and disease chronicity. There is also emerging evidence that airway remodeling is a critical factor in the persistence and severity of asthma. Although airway remodeling in asthma is a new concept, this feature is associated with increased bronchial smooth muscle mass, mucus gland hypertrophy, angiogenesis, thickening of the lamina reticularis and subepithelial fibrosis and deposition of extracellular matrix components. To date, the mechanisms for these structural changes have not been established, but allergic inflammation may contribute to this process by (1) enhanced release of matrix metalloproteinases, (2) generation of fibrogenic cytokines, and (3) increased local generation and deposition of fibronectin in the airway mucosa. Based upon current information and our own preliminary data, it is hypothesized that the airway response to allergen initiates a "vicious cycles" by which (a) airway inflammatory cells (eosinophils and T cells) produce fibrogenic cytokines that, in turn, stimulate fibroblast proliferation and synthesis of fibronectin, and (b), conversely, factors produced by fibroblasts (cytokines, chemokines and fibronectin) promote eosinophilic inflammation in the airway. The end result of this process is structural changes to the airway with persistent airflow obstruction and increased asthma severity. The following protocol is designed to, first, define the role of allergen in the development of cellular inflammation and transition to airway remodeling. To accomplish this specific aim, asthma subjects will be challenged with allergen by segmental bronchoscopy that will be followed by ravage and biopsy, which will be performed immediately, 48 hours, and 7 days post-antigen exposure. These experiments will define the cellular recruitment and generation of inflammatory and growth factor cytokines, as well as production and deposition of extracellular matrix proteins. Second, to establish the relationship between the acute inflammatory response to allergen and resulting structural remodeling of the airway by defining the mechanism(s) by which (a) airway inflammatory cells (eosinophils and T cells) stimulate fibroblast proliferation and synthesis of fibronectin, and (b) fibroblasts, in turn, promote eosinophil inflammation and fibrosis in the airway. These studies will provide new information on the mechanisms by which allergen not only can cause airway inflammation but also lead to structural changes in the airway (i.e. remodeling) that may then lead to persistent airflow obstruction.